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Improving the hole picture: towards a consensus on the mechanism of nuclear transport

Nuclear pore complexes (NPCs) mediate the exchange of materials between the nucleoplasm and cytoplasm, playing a key role in the separation of nucleic acids and proteins into their required compartments. The static structure of the NPC is relatively well defined by recent cryo-EM and other studies....

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Detalles Bibliográficos
Autores principales: Cowburn, David, Rout, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212546/
https://www.ncbi.nlm.nih.gov/pubmed/37099395
http://dx.doi.org/10.1042/BST20220494
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author Cowburn, David
Rout, Michael
author_facet Cowburn, David
Rout, Michael
author_sort Cowburn, David
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description Nuclear pore complexes (NPCs) mediate the exchange of materials between the nucleoplasm and cytoplasm, playing a key role in the separation of nucleic acids and proteins into their required compartments. The static structure of the NPC is relatively well defined by recent cryo-EM and other studies. The functional roles of dynamic components in the pore of the NPC, phenylalanyl-glycyl (FG) repeat rich nucleoporins, is less clear because of our limited understanding of highly dynamic protein systems. These proteins form a ‘restrained concentrate’ which interacts with and concentrates nuclear transport factors (NTRs) to provide facilitated nucleocytoplasmic transport of cargoes. Very rapid on- and off-rates among FG repeats and NTRs supports extremely fast facilitated transport, close to the rate of macromolecular diffusion in cytoplasm, while complexes without specific interactions are entropically excluded, though details on several aspects of the transport mechanism and FG repeat behaviors remain to be resolved. However, as discussed here, new technical approaches combined with more advanced modeling methods will likely provide an improved dynamic description of NPC transport, potentially at the atomic level in the near future. Such advances are likely to be of major benefit in comprehending the roles the malfunctioning NPC plays in cancer, ageing, viral diseases, and neurodegeneration.
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spelling pubmed-102125462023-05-26 Improving the hole picture: towards a consensus on the mechanism of nuclear transport Cowburn, David Rout, Michael Biochem Soc Trans Review Articles Nuclear pore complexes (NPCs) mediate the exchange of materials between the nucleoplasm and cytoplasm, playing a key role in the separation of nucleic acids and proteins into their required compartments. The static structure of the NPC is relatively well defined by recent cryo-EM and other studies. The functional roles of dynamic components in the pore of the NPC, phenylalanyl-glycyl (FG) repeat rich nucleoporins, is less clear because of our limited understanding of highly dynamic protein systems. These proteins form a ‘restrained concentrate’ which interacts with and concentrates nuclear transport factors (NTRs) to provide facilitated nucleocytoplasmic transport of cargoes. Very rapid on- and off-rates among FG repeats and NTRs supports extremely fast facilitated transport, close to the rate of macromolecular diffusion in cytoplasm, while complexes without specific interactions are entropically excluded, though details on several aspects of the transport mechanism and FG repeat behaviors remain to be resolved. However, as discussed here, new technical approaches combined with more advanced modeling methods will likely provide an improved dynamic description of NPC transport, potentially at the atomic level in the near future. Such advances are likely to be of major benefit in comprehending the roles the malfunctioning NPC plays in cancer, ageing, viral diseases, and neurodegeneration. Portland Press Ltd. 2023-04-26 2023-04-26 /pmc/articles/PMC10212546/ /pubmed/37099395 http://dx.doi.org/10.1042/BST20220494 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Articles
Cowburn, David
Rout, Michael
Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title_full Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title_fullStr Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title_full_unstemmed Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title_short Improving the hole picture: towards a consensus on the mechanism of nuclear transport
title_sort improving the hole picture: towards a consensus on the mechanism of nuclear transport
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212546/
https://www.ncbi.nlm.nih.gov/pubmed/37099395
http://dx.doi.org/10.1042/BST20220494
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